There are many prior art processes for preparing dihydroxyquinoline and derivatives thereof.
The oldest method uses Doebuer-Miller's reaction, and is based on melting N-acetylanthranilic acid with a mixture of NaOH, KOH, NaNH.sub.2 at 150.degree. to 190.degree. C. The following reaction equation is illustrative. ##STR2## This is a high yield method but requires NaNH.sub.2, a chemical which is highly hazardous because of (1) Spontaneous explosion of NaNH.sub.2 itself or (2) Occurrences of explosions in case of a trace of water present in the reaction mixture. This process is disclosed in German Pat. No. 117,167.
Another preparative method is based on the cyclization of ethyl N-acetylanthranilate by means of metallic sodium. The yield is relatively low, about 30 to 40 percent of the theory. The method is illustrated by the following equation. ##STR3## A further preparative method is based on the cyclization of the condensation product of 1 mole of ethyl anthranilate with 1 mole of diethylmalonate by means of sodium methoxide, followed by saponification and decarboxylation. This method produces higher yields of dihydroxyquinoline, but of lower purity as a consequence of unclean condensation of malonate with ethyl anthranilate. The following reactions illustrate the process. ##STR4##
In recently issued U.S. Pat. No. 3,642,571, assigned to BASF, there is disclosed the preparation of 2,4-dihydroxyquinolines based on treatment of 2-substituted benzoxazinones-4 with alkali metal alkoxides or sodium piperidine at temperatures from room to about 200.degree. C. ##STR5## R=H, or an electron attracting group (CH.sub.3 --CO--)
The starting benzoxazinone-4 is prepared from anthranilic acid through reaction with acetic anhydride or diketene.
Other recent patents, also assigned to BASF, U.S. Pat. Nos. 3,682,928 and 3,753,991, disclose a process for the production of 2,4-dihydroxyquinoline based on the cyclization of N-acetoacetylanthranilic acid ester with an aqueous solution of 1-10 equivalents of alkali-or alkaline earth hydroxides, followed by deacetylation of the formed 3-acetyl-2,4-dihydroxyquinoline by means of a strong acid such as H.sub.2 SO.sub.4, HCl, HBr, HClO.sub.3 or H.sub.3 PO.sub.4 at a temperature from about 90.degree. to 130.degree. C. U.S. Pat. No. 3,753,991 further discloses the use of a strong base at a temperature of 130.degree. to 190.degree. C. during deacetylation in place of the strong acid.
In both patents the starting N-acetoacetylanthranilic acid ester is made through the reaction of the corresponding alkyl anthranilate with diketene. ##STR6##